title: Do type 1 receptor tyrosine kinases inform treatment choice? A prospectively planned analysis of the TEAM trial.
abstract: BACKGROUND
  Epidermal growth factor receptors contribute to breast cancer relapse during endocrine therapy. Substitution of aromatase inhibitors (AIs) may improve outcomes in HER-positive cancers.
  
  
  METHODS
  Tissue microarrays were constructed. Quantitative analysis of HER1, HER2, and HER3 was performed. Data were analysed relative to disease-free survival and treatment using outcomes at 2.75 and 6.5 years.
  
  
  RESULTS
  Among 4541 eligible samples, 4225 (93%) had complete HER1-3 data. Overall, 5% were HER1-positive, 13% HER2-positive, and 21% HER3-positive; 32% (n=1351) overexpressed at least one HER receptor. In the HER1-3-negative subgroup, the hazard ratio (HR) for upfront exemestane vs tamoxifen at 2.75 years was 0.67 (95% confidence interval (CI), 0.52-0.87), in the HER1-3-positive subgroup, the HR was 1.15 (95% CI, 0.85-1.56). A prospectively planned treatment-by-marker analysis demonstrated a significant interaction between HER1-3 and treatment at 2.75 years (HR=0.58; 95% CI, 0.39-0.87; P=0.008), as confirmed by multivariate regression analysis adjusting for prognostic factors (HR=0.55; 95% CI, 0.36-0.85; P=0.005). This effect was time dependent.
  
  
  CONCLUSIONS
  In the 2.75 years prior to switching patients initially treated with tamoxifen to exemestane, a significant treatment-by-marker effect exists between AI/tamoxifen treatment and HER1-3 expression, suggesting HER expression could be used to select appropriate endocrine treatment at diagnosis to prevent or delay early relapses.
authors.affiliation: 1] Transformative Pathology, Ontario Institute for Cancer Research, Toronto, Canada M5G 0A3 [2] Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh EH4 2XR, UK.
authors.forename: J M S
authors.initials: JM
authors.lastname: Bartlett
authors.forename: C L
authors.initials: CL
authors.lastname: Brookes
authors.forename: T
authors.initials: T
authors.lastname: Piper
authors.forename: C J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: D
authors.initials: D
authors.lastname: Stocken
authors.forename: N
authors.initials: N
authors.lastname: Lyttle
authors.forename: A
authors.initials: A
authors.lastname: Hasenburg
authors.forename: M A
authors.initials: MA
authors.lastname: Quintayo
authors.forename: D G
authors.initials: DG
authors.lastname: Kieback
authors.forename: H
authors.initials: H
authors.lastname: Putter
authors.forename: C
authors.initials: C
authors.lastname: Markopoulos
authors.forename: E M-K
authors.initials: EM
authors.lastname: Kranenbarg
authors.forename: E A
authors.initials: EA
authors.lastname: Mallon
authors.forename: L Y
authors.initials: LY
authors.lastname: Dirix
authors.forename: C
authors.initials: C
authors.lastname: Seynaeve
authors.forename: D W
authors.initials: DW
authors.lastname: Rea
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D011379:Prognosis; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use; D013629:Tamoxifen / Q000627:therapeutic use; D046888:Tissue Array Analysis
chemical_list: D000730:Androstadienes; D047072:Aromatase Inhibitors; D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D066246:ErbB Receptors; C056516:exemestane